Identification of key genes in arrhythmogenic right ventricular cardiomyopathy based on a GEO database chip: a bioinformatics analysis
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摘要: 目的:寻找致心律失常性右室心肌病(ARVC)发病关键基因。方法:从GEO数据库获得人类ARVC现有信息芯片,筛选出ARVC心肌和正常心肌间差异基因。通过David数据库进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路分析,利用String数据库和Cytoscape软件构建蛋白质相互作用(PPI)网络。结果:共鉴定出101个差异基因,包括40个上调基因和61个下调基因。GO分析显示,P<0.01且基因数>10的生物过程(BP)包括炎症反应和信号转导,细胞组分(CC)包括细胞膜、细胞外空间和细胞外区域。KEGG分析显示,P<0.01的通路为肿瘤坏死因子(TNF)信号通路。经过PPI分析筛选得出10个关键基因:白细胞介素6(IL-6)、CCL2、AIF1、CD14、CCR1、FCER1G、FPR1、PTGS2、S100A9和S100A8。结论:ARVC的发生发展可能与炎症机制密切相关,可作为潜在的治疗靶点为ARVC进一步研究提供依据。
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关键词:
- 致心律失常性右室心肌病 /
- 关键基因 /
- GEO数据库 /
- 生物信息分析
Abstract: Objective: To search for the key genes that cause arrhythmogenic right ventricular cardiomyopathy (ARVC).Method: The existing information chip of human ARVC was obtained from the GEO database, and the differential genes between normal cardiac tissues and ARVC cardiac tissues were screened out. Functional annotation of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were conducted through David database, and protein-protein interaction(PPI) network was constructed by using String database and Cytoscape software.Result: A total of 101 differential genes were identified, including 40 up-regulated genes and 61 down-regulated genes. GO analysis showed that the biological process (BP) with P<0.01 and gene number > 10 includes inflammatory response and signal transduction. The cell component (CC) included cell membrane extracel-lular space and extracellular region. KEGG analysis showed that the pathway with P <0.01 was the TNF signaling pathway. After PPI analysis, 10 key genes were identified:IL-6, CCL2, AIF1, CD14, CCR1, FCER1G, FPR1, PTGS2, S100A9 and S100A8.Conclusion: The occurrence and development of ARVC may be closely related to the mechanism of inflammation, which can be used as a potential therapeutic target to provide a basis for further research of ARVC. -
[1] Corrado D, Thiene G.Arrhythmogenic right ventricular cardiomyopathy/dysplasia:clinical impact of molecular genetic studies[J].Circulation, 2006, 113(13):1634-1637.
[2] Mazzanti A, Ng K, Faragli A, et al.Arrhythmogenic right ventricular cardiomyopathy:clinical course and predictors of arrhythmic risk[J].J Am Coll Cardiol, 2016, 68(23):2540-2550.
[3] Tsatsopoulou A.Common presentation of rare diseases:Arrhythmogenic right ventricular cardiomyopathy and its mimics[J].Int J Cardiol, 2018, 257:371-377.
[4] 朱文根, 贺文凤, 洪葵.心律失常基质与致心律失常性右室心肌病[J].临床心血管病杂志, 2015, 31(1):73-76.
[5] Patel H, Shah P, Rampal U, et al.Arrythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and cathecholaminergic polymorphic ventricular tachycardia (CPVT):A phenotypic spectrum seen in same patient[J].J Electrocardiol, 2015, 48(5):874-878.
[6] 范思洋, 姚焰.致心律失常性心肌病诊疗进展[J].心电与循环, 2019, 38(5):376-379.
[7] 马慧慧, 戴霞飞, 李小平.致心律失常性右室心肌病的遗传学研究进展[J].临床心血管病杂志, 2019, 35(2):104-108.
[8] Wang Y, Li C, Shi L, et al.Integrin β1D deficiency-mediated RyR2 dysfunction contributes to catecholamine-sensitive ventricular tachycardia in ARVC[J].Circulation, 2020, 141(18):1477-1493
[9] Gaertner A, Schwientek P, Ellinghaus P, et al.Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy[J].Physiol Genomics, 2012, 44(1):99-109.
[10] Ashburner M, Ball CA, Blake JA, et al.Gene ontology:tool for the unification of biology The Gene Ontology Consortium[J].Nat Genet, 2000, 25(1):25-29.
[11] Shannon P, Markiel A, Ozier O, et al.Cytoscape:A software environment for integrated models of biomolecular interaction networks[J].Genome Res, 2003, 13(11):2498-2504.
[12] Chin CH, Chen SH, Wu HH, et al.cytoHubba:identifying hub objects and sub-networks from complex interactome[J].BMC Syst Biol, 2014, 8 Suppl 4:S11.
[13] Bader GD, Hogue CW.An automated method for finding molecular complexes in large protein interaction networks[J].BMC Bioinformatics, 2003, 4:2.
[14] 付灵华, 洪葵.致心律失常性右心室心肌病与运动[J].临床心血管病杂志, 2017, 33(1):9-12.
[15] Fitzgibbons TP, Czech MP.Epicardial and perivascular adipose tissues and their influence on cardiovascular disease:basic mechanisms and clinical associations[J].J Am Heart Assoc, 2014, 3(2):e000582.
[16] Tsai CT, Wu CK, Lee JK, et al.TNF-α down-regulates sarcoplasmic reticulum Ca2+ ATPase expression and leads to left ventricular diastolic dysfunction through binding of NF-κB to promoter response element[J].Cardiovasc Res, 2015, 105(3):318-329.
[17] Anumonwo JMB, Herron T.Fatty infiltration of the myocardium and arrhythmogenesis[J].Frontiers Physiol, 2018, 9:2.
[18] 刘萧, 郭琳娟, 洪葵.心律失常和心肌病相关趋化因子网络研究进展[J].临床心血管病杂志, 2017, 33(9):901-904.
[19] Campian ME, Verberne HJ, Hardziyenka M, et al.Assessment of inflammation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia[J].Eur J Nucl Med Mol Imaging, 2010, 37(11):2079-2085.
[20] Leuschner F, Courties G, Dutta P, et al.Silencing of CCR2 in myocarditis[J].Eur Heart J, 2015, 36(23):1478-1488.
[21] Sarkar A, Shukla SK, Alqatawni A, et al.The role of allograft inflammatory factor-1 in the effects of experimental diabetes on B cell functions in the Heart[J].Front Cardiovasc Med, 2018, 5:126.
[22] Fukui M, Tanaka M, Toda H, et al.The serum concentration of allograft inflammatory factor-1 is correlated with metabolic parameters in healthy subjects[J].Metabolism, 2012, 61(7):1021-1025.
[23] Lima-Neto LG, Hirata RD, Luchessi AD, et al.CD14 and IL-6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction[J].J Thromb Thrombolysis, 2013, 36(3):332-340.
[24] 王义勇, 麻芳, 黄晖, 等.同型半胱氨酸对泡沫细胞中LXRα-ABCA1信号通路的影响[J].临床心血管病杂志, 2016, 32(7):726-730.
[25] Ohyama K, Matsumoto Y, Takanami K, et al.Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina[J].J Am Coll Cardiol, 2018, 71(4):414-425.
[26] Qin CX, May LT, Li R, et al.Small-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice[J].Nat Commun, 2017, 8:14232.
[27] Chen LT, Jiang CY.Bioinformatics analysis of sex differences in arrhythmogenic right ventricular cardiomyopathy[J].Mol Med Rep, 2019, 19(3):2238-2244.
[28] Vogl T, Tenbrock K, Ludwig S, et al.Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock[J].Nat Med, 2007, 13(9):1042-1049.
[29] Sweet RA, Nickerson KM, Cullen JL, et al.B cell-extrinsic and negatively regulate autoreactive and normal B cell immune responses[J].J Immunol, 2017, 199(3):885-893.
[30] Haudek SB, Trial J, Xia Y, et al.Fc receptor engagement mediates differentiation of cardiac fibroblast precursor cells[J].Proc Nat Acad Sci USA, 2008, 105(29):10179-10184.
[31] Guo Y, Lei I, Tian S, et al.Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming[J].J Biol Chem, 2019, 294(23):9134-9146.
[32] Futamatsu H, Suzuki J, Koga N, et al.A CCR1 antagonist prevents the development of experimental autoimmune myocarditis in association with T cell inactivation[J].J Mol Cell Cardiol, 2006, 40(6):853-861.
[33] Timmers L, Sluijter JP, Verlaan CW, et al.Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig[J].Circulation, 2007, 115(3):326-332.
[34] Streicher JM, Kamei K, Ishikawa TO, et al.Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice[J].J Mol Cell Cardiol, 2010, 49(1):88-94.
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